This is Part 7 of the unabridged original manuscript, submitted by invitation in April 2009 to the theme issue of The Journal of Alzheimer's disease. Edited by the Journal edition was later published and is available upon request (will be published here at a later date)
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Alexei Koudinov, Elena Kezlya, Natalia Koudinova, Temirbolat Berezov Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory mechanism to maintain CNS plasticity under Alzheimer's disease and other neurodegenerative conditions. Journal of Alzheimer’s Disease. 2009 18(2): 381-400. Unabridged Notedited Original Author Edition. Available at: http://alzheimercode.blogspot.com
Article Scheme 1. Conventional neurodegeneration hallmarks are reversible compensatory mechanisms designed by nature, not brain disease endpoints.
This scheme was originally developed to illustrate the development of the sporadic forms of Alzheimer’s disease (see detailed original legend for the scheme at neurobiologyoflipids.org/content/1/6 [[16, 16a, 64]]).
Nevertheless, it is applicable with no modification to other nervous system diseases described at length of this article as disorders of cholesterol-mediated neurodegeneration (A).
Moreover, the scheme, is also applied to practically all other neurodegenerative brain diseases. This is because in response on certain disease-specific central event of any type neurodegeneration, affected brain area reacts with an impairment of neurotransmission, synaptic function and plasticity (B).
Therefore, CNS launches standard set of physiological compensatory mechanisms that aim to restore impaired synaptic function and plasticity (C, ticks). Primary cause of a disease (examples are cholesterol homeostasis failure in cholesterol-dependent neurodegeneration (A); and the failure of the forebrain dopamine system in Parkinson’s disease) defines the specificity of an affected brain area, the chemical specificity of the neurotransmission break, and the fine tuning and certain combination of compensatory mechanisms (including discussed herein changes in Amyloid beta biology, neuroskeleton rearrangements and tau phosphorylation, and oxidative stress and lipid peroxidation modulation) and their combination (C), yielding the unique pattern of neurodegenerative markers overlap in different diseases and individual patients (see article text).
It is conceivable that at certain point of a disease’ progression compensatory processes become secondary features of neurodegeneration, attain irreversibility and contribute themselves for the disease pathogenesis and progression. Apparently, this is where amyloid proponents have been researched Alzheimer’s disease for more then two decades. However, the scenario proposed herein implies that battling secondary degenerative features’ sadly has no ability to cure any type neurodegeneration. Our new look on neurodegeneration requires novel focus on drug therapy: a restoration of impaired primary cause that will naturally lead to the reversal of a disease secondary features. Scheme 1 is a new edition of the scheme presented elsewhere [[63, 64]].
References:
16. NV. Koudinova, A. Kontush, TT. Berezov, AR. Koudinov. Amyloid beta, neural lipids, cholesterol and Alzheimer's disease. Neurobiology Lipids (2003) 1:6. Available at neurobiologyoflipids.org/content/1/6/
First published at BMJ netprints:
16a. Alexei Koudinov and Natalia Koudinova. Brain cholesterol pathology is the cause of Alzheimer's disease. Clin Med Health Res (2001) clinmed/2001100005 clinmed/2001100005v1 (November 27, 2001) FullText | Adobe Acrobat .PDF reprint
63. AR. Koudinov, NV. Koudinova. Brain cholesterol pathology is the cause of Alzheimer's disease. Clin Med Health Res (2001) clinmed/2001100005. Available at: http://clinmed.netprints.org/cgi/content/full/2001100005v1
64. AR. Koudinov, NV. Koudinova. Cholesterol, synaptic function and Alzheimer's disease. Pharmacopsychiatry (2003) S36: 107-12.
Link to this publication: alzheimers-markers-are-compensatory.html
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